Matrix metalloproteinase-10 (MMP-10) is a zinc-dependent endopeptidase involved in regulating a wide range of biologic processes, such as apoptosis, cell proliferation, and tissue remodeling. However, the role of MMP-10 in the pathogenesis of acute kidney injury (AKI) is unknown. In this study, we show that MMP-10 was upregulated in the kidneys and predominantly localized in the tubular epithelium in various models of AKI induced by ischemia/reperfusion (IR) or cisplatin. Overexpression of exogenous MMP-10 ameliorated AKI, manifested by decreased serum creatinine, blood urea nitrogen, tubular injury and apoptosis, and increased tubular regeneration. Conversely, knockdown of endogenous MMP-10 expression aggravated kidney injury. Interestingly, alleviation of AKI by MMP-10 in vivo was associated with the activation of epidermal growth factor receptor (EGFR) and its downstream AKT and extracellular signal-regulated kinase-1 and 2 (ERK1/2) signaling. Blockade of EGFR signaling by erlotinib abolished the MMP-10-mediated renal protection after AKI. In vitro, MMP-10 potentiated EGFR activation and protected kidney tubular cells against apoptosis induced by hypoxia/reoxygenation or cisplatin. MMP-10 was colocalized with heparin-binding EGF-like growth factor (HB-EGF) in vivo and activated it by a process of proteolytical cleavage in vitro. These studies identify HB-EGF as a previously unrecognized substrate of MMP-10. Our findings also underscore that MMP-10 can protect against AKI by augmenting EGFR signaling, leading to promotion of tubular cell survival and proliferation after injury.Exocytosis is a crucial cellular process involved in the release of neural transmitters or signaling hormones, and disposal of waste or toxic materials. The relationship between structural transition and temporal progression of this process is poorly understood, partly due to lack of adequate tools to resolve such dynamic structures at sufficient resolution in 3D. Exocytosis can be hijacked by some viruses, exemplified by the widely used model α-herpesvirus pseudorabies virus (PRV), which relies on exocytosis for trans-synaptic spread across neurons. Here, we have used cryo electron tomography (cryoET) to capture 199 events of PRV exocytosis from cultured hippocampal neurons. We established cumulative frequency analysis to estimate the relative duration of an exocytosis stage based on the frequency of observed viral particles at that stage. This analysis revealed that PRV exocytosis is biphasic, including a fast, "release phase" driven by fusion proteins and fused membranes, and a slow, "recovery phase" driven by flattening of curved membranes. The biphasic property of exocytosis discovered here appears to be conserved for membrane fusion during viral entry, and our approach of cumulative frequency analysis should have general utility for characterizing other membrane fusion events.Pyroptosis is a novel type of programmed cell death associated with the pathogenesis of many inflammatory diseases. Docosahexaenoic acid (DHA) and Arachidonic acid (AA) is widely involved in inflammatory pathological processes. However, the effect and mechanism of DHA and AA on pyroptosis in Kupffer cells are poorly understood. The present study demonstrated that DHA and AA ameliorated lipopolysaccharide (LPS)-induced Kupffer cells pyroptosis by reversing the increased expression of NLRP3 inflammasome complex, GSDMD, IL-1β, IL-18, and PI-stained positive rate. Next, the study revealed that GPR120 silencing eliminated the anti-pyroptosis of DHA and AA in LPS-induced Kupffer cells, suggesting that DHA and AA exerted their effect through GPR120 signaling. Importantly, GPR120 endocytose and binds to NLRP3 under LPS stimulation. Furthermore, co-immunoprecipitation showed that DHA and AA promoted the interaction between GPR120 and NLRP3 in LPS-exposed Kupffer cells, thus inhibiting the self-assembly of NLRP3 inflammasome complex. Finally, the study verified that DHA and AA alleviated hepatic injury through inhibiting Kupffer cells pyroptosis in vivo. The findings indicated that DHA and AA alleviated LPS-induced Kupffer cells pyroptosis via GPR120 interaction with NLRP3, it might become a potential therapeutic approach hepatic injury.The biological clock is an endogenous biological timing system, which controls metabolic functions in almost all organs. Nutrient metabolism, substrate processing, and detoxification are circadian controlled in livers. However, how the clock genes respond to toxins and influence toxicity keeps unclear. We identified the clock gene Per1 was specifically elevated in mice exposed to toxins such as carbon tetrachloride (CCl4). Mice lacking Per1 slowed down the metabolic rate of toxins including CCl4, capsaicin, and acetaminophen, exhibiting relatively more residues in the plasma. Liver injury and fibrosis induced by acute and chronic CCl4 exposure were markedly alleviated in Per1-deficient mice. These processes involved the binding of PER1 protein and hepatocyte nuclear factor-1alpha (HNF-1α), which enhances the recruitment of HNF-1α to cytochrome P450 2E1 (Cyp2e1) promoter and increases Cyp2e1 expression, thereby promoting metabolism for toxins in the livers. https://www.selleckchem.com/products/r16.html These results indicate that PER1 mediates the metabolism of toxins and appropriate suppression of Per1 response is a potential therapeutic target for toxin-induced hepatotoxicity.Sensory over-responsivity (SOR), extreme sensitivity to or avoidance of sensory stimuli (e.g., scratchy fabrics, loud sounds), is a highly prevalent and impairing feature of neurodevelopmental disorders such as autism spectrum disorders (ASD), anxiety, and ADHD. Previous studies have found overactive brain responses and reduced modulation of thalamocortical connectivity in response to mildly aversive sensory stimulation in ASD. These findings suggest altered thalamic sensory gating which could be associated with an excitatory/inhibitory neurochemical imbalance, but such thalamic neurochemistry has never been examined in relation to SOR. Here we utilized magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging to examine the relationship between thalamic and somatosensory cortex inhibitory (gamma-aminobutyric acid, GABA) and excitatory (glutamate) neurochemicals with the intrinsic functional connectivity of those regions in 35 ASD and 35 typically developing pediatric subjects. Although there were no diagnostic group differences in neurochemical concentrations in either region, within the ASD group, SOR severity correlated negatively with thalamic GABA (r?=?-0.